Efficient drug-delivery using magnetic nanoparticles — biodistribution and therapeutic effects in tumour bearing rabbits

• Published in: Nanomedicine Vol. 9; no. 7; pp. 961 - 971
• Main Authors: Tietze, Rainer, Lyer, Stefan, Dürr, Stephan, Struffert, Tobias, Engelhorn, Tobias, Schwarz, Marc, Eckert, Elisabeth, Göen, Thomas, Vasylyev, Serhiy, Peukert, Wolfgang, Wiekhorst, Frank, Trahms, Lutz, Dörfler, Arnd, Alexiou, Christoph
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013
• Subjects: Animals; Cancer; Drug delivery; Drug Delivery Systems; Female; Internal Medicine; Magnetic drug targeting; Magnetite Nanoparticles - chemistry; Magnetite Nanoparticles - ultrastructure; Mitoxantrone - chemistry; Mitoxantrone - pharmacology; Mitoxantrone - therapeutic use; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Particle Size; Rabbits; Radiography; Spectrophotometry, Infrared; SPIONs; Tissue Distribution; Tumour therapy; Drug delivery; SPIONs; Tumour therapy; Magnetic drug targeting; Cancer
• ISSN: 1549-9634; 1549-9642; 1549-9642
• DOI: 10.1016/j.nano.2013.05.001

To treat tumours efficiently and spare normal tissues, targeted drug delivery is a promising alternative to conventional, systemic administered chemotherapy. Drug-carrying magnetic nanoparticles can be concentrated in tumours by external magnetic fields, preventing the nanomaterial from being cleared by metabolic burden before reaching the tumour. Therefore in Magnetic Drug Targeting (MDT) the favoured mode of application is believed to be intra-arterial. Here, we show that a simple yet versatile magnetic carrier-system (hydrodynamic particles diameter <200nm) accumulates the chemotherapeutic drug mitoxantrone efficiently in tumours. With MDT we observed the following drug accumulations relative to the recovery from all investigated tissues: tumour region: 57.2%, liver: 14.4%, kidneys: 15.2%. Systemic intra-venous application revealed different results: tumour region: 0.7%, liver: 14.4 % and kidneys: 77.8%. The therapeutic outcome was demonstrated by complete tumour remissions and a survival probability of 26.7% (P=0.0075). These results are confirming former pilot experiments and implying a milestone towards clinical studies. This team of investigators studied drug carrying nanoparticles for magnetic drug targeting (MDT), demonstrating the importance of intra-arterial administration resulting in improved clinical outcomes in the studied animal model compared with intra-venous. Super Paramagnetic Iron Oxide Nanoparticles (SPION) are coated with lauric acid and functionalized with mitoxantrone. They are characterized using various physical methods and applied to experimental rabbits. A comprehensive biodistribution study was correlated to the therapeutic investigations. The biological outcome if applying Magnetic Drug Targeting (MDT) exhibits complete tumour remissions in a series of treated animals. [Display omitted]